Abstract
Lactate dehydrogenase A (LDHA) is involved in a variety of cancers. The purpose of this study was to investigate the expression, prognostic roles and function of LDHA in breast cancer. We found that LDHA was upregulated in both breast cancer cell lines and clinical specimens using quantitative real-time PCR (qRT-PCR). Immunohistochemistry (IHC) analysis of tissue microarrays (TMAs) showed that high LDHA expression was associated with cell proliferation, metastasis and poor patient overall survival (OS) and disease free survival (DFS). Furthermore, we found that LDHA promoted glycolysis and cell proliferation in vitro and in vivo. We also performed luciferase reporter assays and found that LDHA was a direct target of miR-34a. Repression of LDHA by miR-34a suppressed glycolysis and cell proliferation in breast cancer cells in vitro. Our findings provide clues regarding the role of miR-34a as a tumor suppressor in breast cancer through the inhibition of LDHA both in vitro and in vivo. Targeting LDHA through miR-34a could be a potential therapeutic strategy in breast cancer.
Highlights
Known oncogenes and deacetylases, such as MYC, HIF-1α, forkhead box protein M1 (FOXM1), Krüppel-like factor 4 (KLF4), and SIRT223,24,28,33–35
LDHA is reported to be upregulated in many cancers, including gastric cancer, renal cell carcinoma, pancreatic cancer, esophageal squamous cell carcinoma and others. quantitative real-time PCR (qRT-PCR) analysis was used to detect the expression of LDHA in 9 different mammary cell lines, including the human mammary epithelial (HME) cell line (MCF-10A) and human breast cancer cell lines (SKBR3, BT-474, BT-483, T47D, MCF-7, MDA-MB-468, MDA-MB-231, MDA-MB-435)
Compared with HME cell line (MCF-10A), we found that LDHA was upregulated in human breast cancer cell lines, especially in BT-483, MDA-MB-435, MDA-MB-231 and MDA-MB-468 (Fig. 1A)
Summary
Known oncogenes and deacetylases, such as MYC, HIF-1α , forkhead box protein M1 (FOXM1), Krüppel-like factor 4 (KLF4), and SIRT223,24,28,33–35. All of these findings indicate that LDHA could be a novel therapeutic target. Several miRNAs have been shown to play important roles in metabolism in cancer[36]. The mechanisms of miRNAs in glycolysis are unclear. We investigate the roles of LDHA and the association of miR-34a and LDHA in breast cancer
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